PROJECT SUMMARY: PATHOGEN ASSOCIATED MALIGNANCIES (PAM) The overall focus of this program is to study pathogen-associated malignancies (PAM) to better prevent, diagnose, and treat these cancers. We will place an emphasis on studying host-pathogen interactions to identify novel vulnerabilities caused by the pathogens and will use this information to design prevention or treatment strategies. We will focus on anogenital and oropharyngeal cancers caused by human papillomaviruses (HPV), Merkel cell carcinoma (MCC) caused by Merkel cell polyomavirus (MCPyV), gastric cancers caused by Helicobacter pylori (H. pylori), Kaposi sarcoma and other lymphomas caused by Kaposi sarcoma herpesvirus (KSHV), liver cancers caused by hepatitis B and C viruses (HBV, HCV), and both lymphomas and epithelial cancers caused by Epstein Barr virus (EBV). Additionally, we will study the role that specific bacteria or the microbiome play in promoting cancer and in modifying response to treatment modalities. The specific aims of the program are (1) to study host-pathogen interactions of PAMs to identify mechanisms of cancer induction and exploitable vulnerabilities, (2) to support translational studies of PAMs in preclinical and clinical settings that can inform the design of better prevention or therapeutic strategies, and (3) to implement effective public health measures to eliminate PAMs and adapt the advances in cancer research made in resource-rich countries to address the cancer burdens of low income countries. The PAM Program currently has 37 members with 14 members having primary appointments at Fred Hutch, 22 members at University of Washington, and 1 member at Seattle Children?s. The current research support of PAM members is $26.4M (direct costs), of which $7.6M is peer-reviewed funding, including $2M from the NCI. The PAM program published a total of 377 papers in the last grant period, of which 16% were intra- programmatic, 44% were inter-programmatic, 52% were inter-institutional, and 45% had external co-authors. Program members have utilized all 12 of the Consortium Shared Resources. This P30 grant also assists this program by providing administrative and logistical support for PAM meetings, pilot funding for new research projects, and recruitment resources for new faculty.